Chloroacetic anhydride → (S)-8-chloro-1-(5-chloromethyl-1,2,4-oxadiazol-3-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one

HRID 1378201Notes

Reaction equation

HRID 1378201 reaction equation
[Cl:1][C:2]1[C:7]2[C:8](=[O:23])[N:9]3[CH2:22][CH2:21][CH2:20][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16](=[N:18][OH:19])[NH2:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[Cl:24][CH2:25][C:26](OC(=O)CCl)=O>CN(C)C=O>[Cl:1][C:2]1[C:7]2[C:8](=[O:23])[N:9]3[CH2:22][CH2:21][CH2:20][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]3[N:17]=[C:26]([CH2:25][Cl:24])[O:19][N:18]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 10946Chloroacetic anhydrideHCID 53703069(S)-8-chloro-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxamidoxime

Product 1

HCID 54468676(S)-8-chloro-1-(5-chloromethyl-1,2,4-oxadiazol-3-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-oneYield 75.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of 7.07 g (21.3 mmol) of (S)-8-chloro-9-oxo-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxamidoxime in 50 ml of N,N-dimethylformamide was treated with 4.0 g (23.4 mmol) of chloroacetic anhydride. The yellow solution obtained was stirred at 105° for 2 hrs. and then completely freed from the solvents. The oily product was chromatographed over silica gel with methylene chloride/methanol 9:1 as the eluent and the oily product obtained was recrystallized from ethyl acetate/ether. The mother liquor was concentrated, the residue was again chromatographed over silica gel with acetonitrile as the eluent and the additional portion of product obtained was recrystallized from ethyl acetate/ether. There were obtained a total of 6.27 g (75%) of (S)-8-chloro-1-(5-chloromethyl-1,2,4-oxadiazol-3-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one as white crystals; m.p. 184°-186° and [α]D20 =+36.1° (MeOH, c=1%).

Workup

  1. customThe yellow solution obtained
  2. customThe oily product was chromatographed over silica gel with methylene chloride/methanol 9:1 as the eluent
  3. customthe oily product obtained
  4. customwas recrystallized from ethyl acetate/ether
  5. concentrationThe mother liquor was concentrated
  6. customthe residue was again chromatographed over silica gel with acetonitrile as the eluent
  7. customthe additional portion of product obtained
  8. customwas recrystallized from ethyl acetate/ether

Sources & evidence

ORD record
ord-f07d637f349747d09dc0314f5a50fe28
Source dataset
uspto-grants-1997_09
Patent number
US05665718

Reaction notes

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